1. Field of the Invention
This invention relates to 3-alkylated-8-aminated-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines useful as strong analgesics and to intermediates useful in the preparation thereof.
2. Description of the Prior Art
The structural formula and numbering 1,2,3,4,5,6,-hexahydro-2,6-methano-3-benzazocine are shown in Formula A. An alternative name for the same compound is 6,7-benzomorphan, whose numbering is shown in Formula B. ##STR1##
Pentazocine having Formula C (Merck Index, Ninth Edition, Monograph 6921; U.S. Pat. No. 3,250,678) is an analgesic in current clinical use. Cyclazocine having Formula D (Merck Index, Ninth Edition, Monograph 2710; U.S. Pat. No. 3,372,165) is an experimental clinical analgesic. ##STR2##
Jacobson and May (J. Med. Chem., Vol. 8, 1965, pp. 563-566) describes two 2'-amino-6,7-benzomorphans having Formulas E and F, the corresponding 2'-nitro-6,7-benzomorphans, and the 2'-nitro-6,7-benzomorphan corresponding to Formula G. ##STR3## The five compounds together with a 2'-chloro-6,7-benzomorphan and a 2'-fluoro-6,7-benzomorphan were tested for analgetic activity and the following conclusion was reached:
It is apparent that replacement of the 2'--OH or 2'--H with nitro, amino, chloro, and fluoro considerably reduces analgetic effectiveness.
U.S. Pat. No. 3,833,595 describes the 2'-amino-6,7-benzomorphan having Formula G and the corresponding 2'-nitro-6,7-benzomorphan as intermediates for conversion of 2'-hydrogen to 2'-hydroxy and the 2'-nitro-6,7-benzomorphan of Formula H as an intermediate for 2-fluorobenzoylpropylation.